Product Description

COMPOSITION: Each tablet contains:-

Rosuvastatin 10 mg

Fenofibrate 160 mg

M.O.A. :

Fenofibrate belongs to a class of drugs called as fibrates or fibric acid derivatives. It works by increasing the action of enzyme lipoprotein lipase which decreases the level of fats (triglycerides) in the blood.

Rosuvastatin belongs to a group of medications called statins (lipid-lowering agents) or HMG CoA reductase inhibitors. It acts by blocking the enzyme HMG CoA reductase and formation of cholesterol, thus, lowering the blood lipid levels.

PHARMACOLOGY:

Rosuvastatin is a fully synthetic competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. Triglycerides (TG) and cholesterol in the liver are incorporated, with apolipoprotein B (ApoB), into very low density lipoprotein (VLDL) and released into the plasma for delivery to peripheral tissues. VLDL particles are TG-rich. Cholesterol-rich low density lipoprotein (LDL) is formed from VLDL and is cleared primarily through the high affinity LDL receptor in the liver. Rosuvastatin produces its lipidmodifying effects in two ways; it increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles. High density lipoprotein (HDL), which contains ApoA-I, is involved, amongst other functions, in transport of cholesterol from tissues back to the liver (reverse cholesterol transport). The involvement of LDL-C in atherogenesis has been well documented. Epidemiological studies have established that high LDL-C and TG and low HDL-C and ApoA-I have been linked to a higher risk of cardiovascular disease. Intervention studies have shown the benefits on mortality and CV event rates of lowering LDL-C and TG or raising HDL-C. More recent data has linked the beneficial effects of HMG-CoA reductase inhibitors to the lowering of non-HDL-C (i.e. all circulating cholesterol not in HDL) and ApoB or reducing the ApoB/ApoA-I ratio.

Pharmacokinetics:

A study was conducted which compared this product with the reference product and the two products were shown to be bioequivalent. In this study, the 90% confidence intervals for the ratio of AUC0-t and Cmax were both found to be between 80% and 125%.

Absorption

Peak plasma levels occur 5 hours after dosing. Absorption increases linearly over the dose range. Absolute bioavailability is 20%. The half-life is 19 hours and does not increase with increasing dose. There is minimal accumulation on repeated once daily dosing.

Distribution

Volume of distribution of rosuvastatin at steady state is approximately 134 litres. Rosuvastatin is approximately 90% bound to plasma proteins, mostly albumin.

Metabolism

Rosuvastatin is not extensively metabolized; approximately 10% of a radio-labelled dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin, which is formed principally by cytochrome P450 2C9 and in vitro studies have demonstrated that N-desmethyl rosuvastatin has approximately one-sixth to one-half the HMG-CoA reductase inhibitory activity of rosuvastatin. Overall, greater than 90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by rosuvastatin.

Excretion

Rosuvastatin undergoes limited metabolism (approximately 10%), mainly to the N-desmethyl form, and 90% is eliminated as unchanged drug in the faeces, with the remainder being excreted in the urine.